The overall aim of this project is to investigate the familial aggregation of Obsessive-Compulsive Disorder (OCD) and to examine the nature of the genetic factors contributing to its etiology. Specifically, we propose to seek out specific monogenic mechanisms that predispose individuals to OCD; to study further the coexistence of other mental disorders in patients affected with OCD and the incidence of OCD and other psychiatric diseases in the first and second degree relatives of these patients in order to study ethnic and gender differences in the etiology and symptomatology of OCD. We will also investigate the effects of gender on symptom presentation. Patients and their families will be ascertained through the Tulane Medical Center OCD clinic in New Orleans, Louisiana and through the clinics at the Instituto Mexicano de Psiquiatria in Mexico City, Mexico. We will search for an underlying genetic liability for OCD by examining the inheritance of the quantitative measures of symptom severity (using the results of the Yale-Brown Obsessive-Compulsive Scale and the NIMH Global Obsessive Compulsive Scales). It is very likely that Obsessive-Compulsive Disorder is a genetically heterogeneous disease. We will use segregation analyses to try to sort out the various forms of OCD and to determine its etiological relationship to Tourette's syndrome, chronic motor tics, major depression, anxiety disorders, substance abuse and other psychiatric disorders. These analyses will generate new hypotheses for future studies. Linkage analysis will be done on families obtained though the Mexican clinics to seek out the chromosomal location of the gene (or genes) contributing to OCD. There are over four million sufferers of OCD in the United States. The results of this study should lead to better genetic counseling, better treatment, and a better understanding of the biological mechanisms underlying this debilitating disease.